Immune checkpoint inhibitor-related myositis and myocarditis in patients with cancer

Touat, Mehdi; Maisonobe, Thierry; Knauß, Samuel; Salem, Omar Ben Hadj; Hervier, B.; Auré, Karine; Szwebel, Tali‐Anne; Kramkimel, N.; Lethrosne, Claire; Bruch, Jean-Frédéric; Laly, Pauline; Cadranel, J.; Weiss, Nicolas; Béhin, Anthony; Allenbach, Yves; Benveniste, Olivier; Lenglet, Timothée; Psimaras, Dimitri; Stenzel, Werner; Léonard-Louis, Sarah

doi:10.1212/wnl.0000000000006124

Cited by 259 publications

(322 citation statements)

References 44 publications

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“…Patients formerly reported as having ICI‐induced myositis and myasthenia gravis show remarkably homogeneous and unique clinicopathological features. Touat and colleagues suggested a new entity of the myositis spectrum that allows overlap of such features . Kao and colleagues recently described many ICI‐induced myopathic cases and found unique subtypes showing oculobulbar involvement and dyspnea resembling myasthenia gravis .…”

Section: Discussionmentioning

confidence: 99%

“…Touat and colleagues suggested a new entity of the myositis spectrum that allows overlap of such features. 1 Kao and colleagues recently described many ICI-induced myopathic cases and found unique subtypes showing oculobulbar involvement and dyspnea resembling myasthenia gravis. 9 Based on the findings in our case, we speculate that diaphragm failure may be an essential characteristic in these severe subtypes.…”

Section: Discussionmentioning

confidence: 99%

“…Myasthenia gravis with myositis or rhabdomyolysis induced by administration of immune checkpoint inhibitors (ICIs) was reported as a fatal immune-related adverse event (irAE). 1 The cause of death was described as "myasthenic crisis". However, multiple factors may contribute to respiratory deterioration, especially severe diaphragm involvement.…”

Section: Introductionmentioning

confidence: 99%

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Diaphragm involvement in immune checkpoint inhibitor‐related myositis

et al. 2019

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Diaphragm involvement in immune checkpoint inhibitor‐related myositis

et al. 2019

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“…Other patients present with a primarily myopathic phenotype. In these patients, muscle biopsy findings range from nonspecific myopathic abnormalities to necrotizing myopathy, granulomatous myopathy, or dermatomyositis . Both oculomotor and bulbar weakness have been identified in ICI‐associated myopathy patients in the absence of a decrement on low‐frequency RNS.…”

Section: Acquired Neuromuscular Junction Disorders With Coexisting Mymentioning

confidence: 99%

“…Both oculomotor and bulbar weakness have been identified in ICI‐associated myopathy patients in the absence of a decrement on low‐frequency RNS. These features alone therefore do not reliably indicate the presence of myasthenia in ICI‐treated patients . While ICI‐induced neuromuscular complications may respond to discontinuation of the precipitating agent and immunomodulatory treatment, they are associated with high rates of morbidity and mortality as a result of cancer recurrence, myocarditis or the neuromuscular disorders themselves, particularly respiratory compromise due to myasthenia gravis or myopathy …”

Section: Acquired Neuromuscular Junction Disorders With Coexisting Mymentioning

confidence: 99%

Trouble at the junction: When myopathy and myasthenia overlap

2019

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Although myopathies and neuromuscular junction disorders are typically distinct, their coexistence has been reported in several inherited and acquired conditions. Affected individuals have variable clinical phenotypes but typically display both a decrement on repetitive nerve stimulation and myopathic findings on muscle biopsy. Inherited causes include myopathies related to mutations in BIN1, DES, DNM2, GMPPB, MTM1, or PLEC and congenital myasthenic syndromes due to mutations in ALG2, ALG14, COL13A1, DOK7, DPAGT1, or GFPT1. Additionally, a decrement due to muscle fiber inexcitability is observed in certain myotonic disorders. The identification of a defect of neuromuscular transmission in an inherited myopathy may assist in establishing a molecular diagnosis and in selecting patients who would benefit from pharmacological correction of this defect. Acquired cases meanwhile stem from the co‐occurrence of myasthenia gravis or Lambert‐Eaton myasthenic syndrome with an immune‐mediated myopathy, which may be due to paraneoplastic disorders or exposure to immune checkpoint inhibitors.

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Expert Perspective: Immune Checkpoint Inhibitors and Rheumatologic Complications

Cappelli

Bingham

2021

Arthritis & Rheumatology

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Rheumatologists increasingly receive consults for patients treated with immune checkpoint inhibitors (ICIs) for cancer. ICIs can cause inflammatory syndromes known as immune-related adverse events (IRAEs). Several rheumatic IRAEs have been reported, including inflammatory arthritis, polymyalgia rheumatica, and myositis. For patients who present with musculoskeletal symptoms while receiving ICI therapy, it is important to have an algorithm for evaluation. The differential diagnosis includes a range of musculoskeletal syndromes, such as crystalline arthritis, mechanical issues, and osteoarthritis, in addition to IRAEs. After diagnosing a rheumatic IRAE, rheumatologists must work with the patient and the oncologist to form a treatment plan. Treatment of IRAEs is guided by severity. Evidence for management is limited to observational studies. Inflammatory arthritis and polymyalgia rheumatica are treated with nonsteroidal antiinflammatory drugs in mild cases, glucocorticoids for moderate-to-severe cases, and sometimes require other disease-modifying antirheumatic drugs. Myositis due to ICIs can be accompanied by myocarditis or myasthenia gravis. Glucocorticoids and withholding the ICI are usually required to treat myositis; some patients with severe myositis require intravenous immunoglobulin or plasmapheresis. Further research is needed to optimize treatment of IRAEs that does not compromise the antitumor effect of ICIs. Clinical challenge You receive a consult from a local oncologist. A 65-yearold man with a history of knee osteoarthritis (OA) who had previously undergone total joint arthroplasty of the left knee and is being treated with nivolumab (anti-programmed death 1 [anti-PD-1] monoclonal antibody) for non-small cell lung cancer has new symptoms of severe aching in his arms and legs, with limited mobility. The oncologist does not localize symptoms to the joints and/or muscles but notes that the patient is having trouble doing chores around the house such as cleaning and cooking.

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Immune checkpoint inhibitor-related myositis and myocarditis in patients with cancer

Abstract: irMyositis presents with remarkably homogeneous and unique clinicopathologic features, expanding the nosologic spectrum of inflammatory myopathies in patients with cancer. ICI withdrawal and treatment with corticosteroids improve outcome.

Cited by 259 publications

References 44 publications

Diaphragm involvement in immune checkpoint inhibitor‐related myositis

Diaphragm involvement in immune checkpoint inhibitor‐related myositis

Trouble at the junction: When myopathy and myasthenia overlap

Expert Perspective: Immune Checkpoint Inhibitors and Rheumatologic Complications

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